Infectious Disease and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC, Canada.
Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.
Front Immunol. 2022 Feb 16;13:820350. doi: 10.3389/fimmu.2022.820350. eCollection 2022.
Growth differentiation factor 15 (GDF-15) is a transforming growth factor (TGF)-β superfamily cytokine that plays a central role in metabolism regulation. Produced in response to mitochondrial stress, tissue damage or hypoxia, this cytokine has emerged as one of the strongest predictors of disease severity during inflammatory conditions, cancers and infections. Reports suggest that GDF-15 plays a tissue protective role sympathetic and metabolic adaptation in the context of mitochondrial damage, although the exact mechanisms involved remain uncertain. In this review, we discuss the emergence of GDF-15 as a distinctive marker of viral infection severity, especially in the context of COVID-19. We will critically review the role of GDF-15 as an inflammation-induced mediator of disease tolerance, through metabolic and immune reprogramming. Finally, we discuss potential mechanisms of GDF-15 elevation during COVID-19 cytokine storm and its limitations. Altogether, this cytokine seems to be involved in disease tolerance to viral infections including SARS-CoV-2, paving the way for novel therapeutic interventions.
生长分化因子 15（GDF-15）是转化生长因子（TGF）-β超家族细胞因子，在代谢调节中发挥核心作用。该细胞因子在应对线粒体应激、组织损伤或缺氧时产生，已成为炎症、癌症和感染等疾病严重程度的最强预测因子之一。有报道称，GDF-15 在涉及线粒体损伤的情况下，通过交感神经和代谢适应发挥组织保护作用，但具体涉及的机制仍不确定。在这篇综述中，我们讨论了 GDF-15 作为病毒感染严重程度的独特标志物的出现，特别是在 COVID-19 背景下。我们将通过代谢和免疫重编程，批判性地回顾 GDF-15 作为炎症诱导的疾病耐受介质的作用。最后，我们讨论了 COVID-19 细胞因子风暴期间 GDF-15 升高的潜在机制及其局限性。总之，这种细胞因子似乎参与了包括 SARS-CoV-2 在内的病毒感染的疾病耐受，为新的治疗干预铺平了道路。
